Abstract
1. The present study was designed to determine whether naftidrofuryl oxalate exerts a possible therapeutic effect on brain energy metabolism impaired by microsphere-induced cerebral embolism in vitro. 2. Injection of microspheres into the right carotid canal resulted in a decrease in tissue high-energy phosphates both in the right and left hemispheres, and an increase in tissue lactate in the right hemisphere, on the 3rd and the 5th day after the embolism. The embolism also induced a marked reduction in mitochondrial oxidative phosphorylation ability and succinate dehydrogenase activity. The results suggest that severe ischaemia was induced in the brain by the microsphere administration. 3. Treatment of microsphere-injected rats with naftidrofuryl oxalate (15 mg kg-1) for 3 or 5 days elicited a significant recovery of tissue high-energy phosphate and lactate levels. The recovery was associated with a significant restoration of mitochondrial succinate dehydrogenase activity on the both days and of mitochondrial oxidative phosphorylation rate on the 5th day. 4. The results suggest that naftidrofuryl oxalate is beneficial in the recovery of cerebral energy metabolism impaired by microsphere-induced cerebral ischaemia, presumably through a mechanism involving its direct effect on the cerebral mitochondrial enzyme activities.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Crowe W., Mayevsky A., Mela L. Ion transport and energy metabolism in brain. Neurol Res. 1981;3(2):107–123. doi: 10.1080/01616412.1981.11739594. [DOI] [PubMed] [Google Scholar]
- Furlow T. W., Jr, Bass N. H. Arachidonate-induced cerebrovascular occlusion in the rat. The role of platelets and aspirin in stroke. Neurology. 1976 Apr;26(4):297–304. doi: 10.1212/wnl.26.4.297. [DOI] [PubMed] [Google Scholar]
- Hagihara Y., Sato M., Takane H., Ota Y. [Effects of naftidrofuryl oxalate on peripheral circulation]. Nihon Yakurigaku Zasshi. 1973 Sep;69(5):721–728. [PubMed] [Google Scholar]
- Kobayashi S., Yamaguchi S., Katsube T., Okada K., Kitani M., Murao M., Tsunematsu T. Effects of naftidrofuryl on the time course of the regional cerebral blood flow in acute ischemic stroke. Arzneimittelforschung. 1984;34(11):1580–1583. [PubMed] [Google Scholar]
- LOWRY O. H., PASSONNEAU J. V., HASSELBERGER F. X., SCHULZ D. W. EFFECT OF ISCHEMIA ON KNOWN SUBSTRATES AND COFACTORS OF THE GLYCOLYTIC PATHWAY IN BRAIN. J Biol Chem. 1964 Jan;239:18–30. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lazarewicz J. W., Strosznajder J., Gromek A. Effects of ischemia and exogenous fatty acids on the energy metabolism in brain mitochondria. Bull Acad Pol Sci Biol. 1972;20(8):599–606. [PubMed] [Google Scholar]
- Ljunggren B., Schutz H., Siesjö B. K. Changes in energy state and acid-base parameters of the rat brain during complete compression ischemia. Brain Res. 1974 Jun 20;73(2):277–289. doi: 10.1016/0006-8993(74)91049-x. [DOI] [PubMed] [Google Scholar]
- McGraw C. P. Experimental cerebral infarctioneffects of pentobarbital in Mongolian gerbils. Arch Neurol. 1977 Jun;34(6):334–336. doi: 10.1001/archneur.1977.00500180028006. [DOI] [PubMed] [Google Scholar]
- Mela L. Mitochondrial function in cerebral ischemia and hypoxia: comparison of inhibitory and adaptive responses. Neurol Res. 1979;1(1):51–63. doi: 10.1080/01616412.1979.11739541. [DOI] [PubMed] [Google Scholar]
- Purshottam T., Ghosh N. C. Effect of acute hypoxia on the enzymes involved in the metabolic and nervous functioning of rat brain. Environ Physiol Biochem. 1975;5(2):73–77. [PubMed] [Google Scholar]
- SLATER E. C., BORNER W. D., Jr The effect of fluoride on the succinic oxidase system. Biochem J. 1952 Oct;52(2):185–196. doi: 10.1042/bj0520185. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takeo S., Miyake K., Minematsu R., Tanonaka K., Konishi M. In vitro effect of naftidrofuryl oxalate on cerebral mitochondria impaired by microsphere-induced embolism in rats. J Pharmacol Exp Ther. 1989 Mar;248(3):1207–1214. [PubMed] [Google Scholar]
- Takeo S., Tanonaka K., Hirano T., Miyake K., Okamoto J. [Cerebroprotective action of naftidrofuryl oxalate. I: Prolongation of survival time and protection of cerebral energy metabolism in bilateral carotid artery-ligated mice]. Nihon Yakurigaku Zasshi. 1988 Apr;91(4):267–273. doi: 10.1254/fpj.91.267. [DOI] [PubMed] [Google Scholar]
- Takeo S., Tanonaka K., Tazuma Y., Miyake K., Murai R. Possible mechanism by which coenzyme Q10 improves reoxygenation-induced recovery of cardiac contractile force after hypoxia. J Pharmacol Exp Ther. 1987 Dec;243(3):1131–1138. [PubMed] [Google Scholar]
- Welsh F. A., Durity F., Langfitt T. W. The appearance of regional variations in metabolism at a critical level of diffuse cerebral oligemia. J Neurochem. 1977 Jan;28(1):71–79. doi: 10.1111/j.1471-4159.1977.tb07710.x. [DOI] [PubMed] [Google Scholar]
- Welsh F. A., Ginsberg M. D., Rieder W., Budd W. W. Deleterious effect of glucose pretreatment on recovery from diffuse cerebral ischemia in the cat. II. Regional metabolite levels. Stroke. 1980 Jul-Aug;11(4):355–363. doi: 10.1161/01.str.11.4.355. [DOI] [PubMed] [Google Scholar]
- Welsh F. A., Sakamoto T., McKee A. E., Sims R. E. Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. J Neurochem. 1987 Sep;49(3):846–851. doi: 10.1111/j.1471-4159.1987.tb00971.x. [DOI] [PubMed] [Google Scholar]